This invention relates generally to the field of measurement transducers, and more specifically, to electronic circuits for glucose content measurement instruments for personal independent use.
Still more particularly, the invention relates to an apparatus for improved safety, flexibility of use, and improved measurement performance, in the near-continual determination of glucose or other molecules in extracellular fluids.
The medical literature indicates the need to have dedicated instruments permitting almost continual measurement of the concentration in a patient""s blood of certain specific molecules, such as glucose, lactate and others. Many such instruments dedicated to these measurements have been developed. One of the most serious drawbacks of prior devices has been the excessive invasiveness of known methods of measurement, which involve the need for direct access to a patient""s blood vessels.
Research performed in this sector has, however, proven the validity of measurements of the concentration of such molecules in extracellular fluids, which measurements can be accurately correlated to the corresponding haematic concentrations.
The growing demand for control and cure of diabetes has led to an increase in the request by medical specialists for miniaturized measurement instruments that can be worn by patients and, which permit almost continual automatic and independent determination of the level of glucose in the blood or in intracellular fluids, for periods of from 24-48 hours to assess the circadian trend of this parameter during the normal behavioral activities of the patient.
Instruments of this type have been described in the literature and have been the subject-matter of patents, such as Italian patents IT1170375 and IT1231916. Such instruments, in fact, have been utilized to obtain measurements of glucose levels in artificial pancreases, as described for example in the article by W. J. Spencerxe2x80x94A review of Programmed Insulin Delivery Systemsxe2x80x94published in the review IEEE Transactions on Biomedical Engineering, vol. BME-28, N.3, March 1981, page 237 ff., in which the measurement apparatus is represented schematically in blocks in FIG. 3 on page 239. There, the measurement section is described to be composed of three blocks, including a glucose measurement sensor, a minicomputer, and a measurement viewing system.
The article by J. C. Pickup and D. Rothwell published in the review Medical and Biological Engineering and Computing, 1984, 22, page 385 ff., paragraph 13 item xe2x80x9cGlucose Sensorsxe2x80x9d, describes two types of sensors to measure the glucose level, one for use implanted subcutaneously and one for extracorporeal use: Both of these solutions have certain advantages and drawbacks, which are briefly discussed below.
The implantable type, which comprises a sensor in direct contact with the extracellular fluids, is mounted on a miniaturized electronic circuit, performs the measurements inside the body of the patient, and transmits the results, in a suitably amplified and encoded form, to the extracorporeal memorization and processing system by means of an electromagnetic coupling, which enables the cutaneous barrier to be passed through without electrical contact, and which also permits the energy required for operation of the electronic circuit to be transferred from outside the body to inside the body.
The type of instrument in the implantable version has the advantage that the patient is totally separated from the external system, but such an instrument can only be applied if a measurement transducer, which is extremely stable over time is available. Although such a solution may be ideal for a therapeutic xe2x80x9cartificial pancreasxe2x80x9d for a single patient, it does not satisfy the clinical requirement of being capable of being fitted and removed after a short time, in order to be used in various patients for diagnostic purposes.
The second type of instrument, although particularly suitable for diagnostic controls, is limited to a few days operating capability, requires transcutaneous access by means of a needle to the bidirectional hydraulic circuit, which is formed using hollow fibres that permit an appropriate fluid solution to be pumped into a semipermeable fibre located in the body of the patient, where, through a filter membrane, the solution can collect the glucose molecules found in the extracellular fluid and convey the fluid sample containing the glucose to the measurement transducer fitted in the portable instrument.
Sampling is performed by means of a pump controlled by a microprocessor, operating according to a resident firmware type program, activated on the basis of choices and parameters selected by an external operator and which, after activation, operates totally automatically until subsequent action by the external operator. The microprocessor is capable of managing the hydraulic sample transfer system, and also of taking measurements, processing and storing them, managing any alarm threshold values, and transferring measurements on request to external computers for permanent storage and any further processing.
From a safety viewpoint, inasmuch as the portable instrument is equipped with a battery-operated power supply, there is no problem of user exposure to a main power supply, although this may become a consideration if using a cable to connect the portable instrument to the external computer, both during the phase in which the physician sets the parameters, and during the phase for transferring the measured values from the instrument on the patient to the external computer.
Safety standards for apparatus of this type, such as the current standards indicated in Japanese Law Decree Feb. 24, 1997 no. 46 and Feb. 26, 1998 no. 95, establish that this type of instrument is in Class IIa, in which there are extremely restrictive limits for leakage currents from the device and into the patient: These limits can be achieved by supplying power to the device through extremely low voltage batteries and using special electronic circuits, which permit limitation of the leakage current through the electrolytic conductor composed of the hydraulic tubes containing the solution pumped into the patient and by limiting the return solution to less than one hundredth of the allowed limit value. However, there remains the issue with regard to any leakage currents possibly carried by the connection cable from or to the external computer. The apparatus of the present invention further overcomes such last-mentioned problem through the use of a non-electrical connection.
With regard to the characteristics of the fluid sample taken for measurement, it is pointed out that this class of instruments is capable of handling complex organic fluid samples of any type, obtained from probes that are implanted transcutaneously, percutaneously, or implantable in the intravascular, subcutaneous or intraperitoneal areas, and also from extracorporeal fluid circuits, such as circuits for dialysis, for blood transfusions, for aphaeresis, and so forth. Moreover, the characteristics of the filters incorporated in the implantable hydraulic system define the dimensional limits of molecules able to be taken and permit the exclusion of any phenomena of interference and pollution of the sensor.
Glucose and lactate are considered to be the preferred analytes for the determination of which the apparatus of the present invention is particularly suitable.
It is a first object of the present invention to propose a new and more efficacious solution to the problem posed by the measurement of analytes found in interstitial fluids.
This object is attained with an apparatus according to the invention, characterised by the use of a pressure transducer for controlling the regularity of measurements and utilizing a transmission system for bidirectional transmission of information between an external computer and a measurement instrument of the second type, equipped with an enzymatic transducer outside the body of the patient.
According to the present invention, the transmission system is capable of guaranteeing total electrical isolation between the patient and external electrical circuits in any condition of use even in the circumstance of continual interfacing during the entire measurement phase.
A preferred embodiment of the apparatus of the present invention also includes the use of an alarm warning system capable of supplying a vibrational signal, which is more easily perceived by hearing-impaired patients, in addition to normal acoustic and luminous signals.
The apparatus of the present invention may be implemented by means of appropriate analog, digital or mixed circuits produced using techniques known in the prior art that use physical components and microprocessor programs, or by means of mixed systems of various types and complexities: These various embodiments are designated hereinafter as the hardware, software and firmware embodiments.